Immunotherapy strategies that involve antibody-induced signaling through antigen-specific T-cell receptors (TCR) have been shown to ameliorate autoimmune disease, probably by regulating the immune response to self-antigens. Parenterally administered anti-CD3 monoclonal antibody (mAb) therapy in particular has been shown to be efficacious in preventing and reversing the onset of diabetes in NOD mice (Chatenoud et al., J. Immunol. 158:2947-2954 (1997); Belghith et al., Nat. Med. 9:1202-1208 (2003)) and in treating subjects with Type I diabetes (Herold et al., N. Engl. J. Med. 346(22)1692-1698 (2002), and to reverse experimental allergic encephalomyelitis (EAE) in Lewis rats with a preferential suppressive effect on T-helper type 1 (Th1) cells, which participate in cell-mediated immunity (Tran et al., Intl. Immunol. 13(9): 1109-1120 (2001)). The FDA has approved Orthoclone OKT®3 (muromonab-CD3; Ortho Biotech Products, Bridgewater, N.J.), a murine anti-CD3 antibody, for intravenous injection for the treatment of graft rejection after transplantation (Chatenoud, Nat. Rev. Immunol. 3:123-132 (2003)).